SYNTHETIC LIPOPEPTIDES INCORPORATED IN LIPOSOMES - IN-VITRO STIMULATION OF THE PROLIFERATION OF MURINE SPLENOCYTES AND IN-VIVO INDUCTION OFAN IMMUNE-RESPONSE AGAINST A PEPTIDE ANTIGEN
I. Fernandes et al., SYNTHETIC LIPOPEPTIDES INCORPORATED IN LIPOSOMES - IN-VITRO STIMULATION OF THE PROLIFERATION OF MURINE SPLENOCYTES AND IN-VIVO INDUCTION OFAN IMMUNE-RESPONSE AGAINST A PEPTIDE ANTIGEN, Molecular immunology, 34(8-9), 1997, pp. 569-576
Amphiphilic lipopeptides, such as Pam(3)CysAlaGly and Pam(3)CysSerSer,
were synthesized and incorporated into liposomes, and their ability t
o induce the proliferation of BALB/c mouse splenocyte was tested in vi
tro. When compared to monophosphoryl lipid A (MPL) the following poten
cy order was found: liposomal lipopeptides > liposomal MPL > free (emu
lsified) lipopeptides. These results strongly depend on the size of th
e vesicles used: a mitogenic effect was observed only with lipopeptide
s incorporated within vesicles of diameter less than or equal to 100nm
while lipopeptides in larger vesicles (diameter approximate to 300 nm
) gave no response. This may be related to the necessity for the lipos
ome-associated lipopeptides to be endocytosed to reach putative intrac
ellular targets. As immunoadjuvanticity seems to be linked to B-lympho
cyte activation, the lipopeptides represent attractive alternatives to
MPL for the realization of completely synthetic liposome-based peptid
e vaccine formulations. This was borne out by showing that Pam(3)CysAl
aGly and Pam(3)CysSerSer, when incorporated in small unilamellar vesic
les carrying a covalently conjugated synthetic peptide of sequence IRG
ERA, corresponding to an epitope of the C-terminal region of histone H
3, were able to induce a potent and long-lasting immune response. (C)
1997 Elsevier Science Ltd.